@article{d18e30b61e574b19921a82f81704c1cc,
title = "Soluble ACE2-mediated cell entry of SARS-CoV-2 via interaction with proteins related to the renin-angiotensin system",
abstract = "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause acute respiratory disease and multiorgan failure. Finding human host factors that are essential for SARS-CoV-2 infection could facilitate the formulation of treatment strategies. Using a human kidney cell line—HK-2—that is highly susceptible to SARS-CoV-2, we performed a genome-wide RNAi screen and identified virus dependency factors (VDFs), which play regulatory roles in biological pathways linked to clinical manifestations of SARS-CoV-2 infection. We found a role for a secretory form of SARS-CoV-2 receptor, soluble angiotensin converting enzyme 2 (sACE2), in SARS-CoV-2 infection. Further investigation revealed that SARS-CoV-2 exploits receptor-mediated endocytosis through interaction between its spike with sACE2 or sACE2-vasopressin via AT1 or AVPR1B, respectively. Our identification of VDFs and the regulatory effect of sACE2 on SARS-CoV-2 infection shed insight into pathogenesis and cell entry mechanisms of SARS-CoV-2 as well as potential treatment strategies for COVID-19.",
keywords = "ACE2, COVID-19, RNAi, sACE2, SARS-CoV-2, vasopressin, virus dependency factor",
author = "Yeung, \{Man Lung\} and Teng, \{Jade Lee Lee\} and Lilong Jia and Chaoyu Zhang and Chengxi Huang and Cai, \{Jian Piao\} and Runhong Zhou and Chan, \{Kwok Hung\} and Hanjun Zhao and Lin Zhu and Siu, \{Kam Leung\} and Fung, \{Sin Yee\} and Susan Yung and Chan, \{Tak Mao\} and To, \{Kelvin Kai Wang\} and Chan, \{Jasper Fuk Woo\} and Zongwei Cai and Lau, \{Susanna Kar Pui\} and Zhiwei Chen and Jin, \{Dong Yan\} and Woo, \{Patrick Chiu Yat\} and Yuen, \{Kwok Yung\}",
note = "Funding Information: This study was partly supported by funding from the Sanming Project of Medicine in Shenzhen, China (SZSM201911014); the Innovation and Technology Fund (ITF) and its commissioned research program of the Food and Health Bureau and Consultancy Service for Enhancing Laboratory Surveillance of Emerging Infectious Diseases and Research Capability on Antimicrobial Resistance of the Department of Health, The Government of the Hong Kong Special Administrative Region, China; the Theme-based Research Scheme, General Research Fund and the Collaborative Research Fund (C5012-15E) of the University Grant Committee; and donations of Michael Seak-Kan Tong, Richard Yu, and Carol Yu, the Shaw Foundation of Hong Kong, May Tam Mak Mei Yin, Lee Wan Keung Charity Foundation Limited, Hong Kong Sanatorium \& Hospital, Hui Ming, Hui Hoy and Chow Sin Lan Charity Fund Limited, Chan Yin Chuen Memorial Charitable Foundation, Marina Man-Wai Lee, the Hong Kong Hainan Commercial Association South China Microbiology Research Fund, the Jessie \& George Ho Charitable Foundation, Perfect Shape Medical Limited, Kai Chong Tong, Foo Oi Foundation Limited, Tse Kam Ming Laurence, Betty Hing-Chu Lee, Ping Cham So, and the Lo Ying Shek Chi Wai Foundation. We also thank the support from the Centre for PanorOmic Sciences, Genomics, and Bioinformatics Core, at the University of Hong Kong. The funding sources had no role in the study design, data collection, analysis, interpretation, or writing of the paper. Conceptualization, M.L.Y. and J.L.L.T.; infection experiments, M.L.Y. L.J. and C.Z.; sample coordination and preparation, C.H. J.-P.C. R.Z. Z.C. H.Z. K.-H.C. K.K.-W.T. J.F.-W.C. L.Z. S.Y. T.M.C. Z.C. S.K.P.L. S.-Y.F. and D.-Y.J.; literature review, M.L.Y. J.L.L.T. and K.-Y.Y.; manuscript preparation, M.L.Y. J.L.L.T. D.-Y.J. and K.-Y.Y.; bioinformatics analysis, M.L.Y. and J.L.L.T.; annotation and interactive map preparation, M.L.Y. and J.L.L.T; work supervision, M.L.Y. J.L.L.T. P.C.Y.W. and K.-Y.Y. J.F.-W.C. has received travel grants from Pfizer Corporation Hong Kong and Astellas Pharma Hong Kong Corporation Limited and was an invited speaker for Gilead Sciences Hong Kong Limited and Luminex Corporation. The other authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = apr,
day = "15",
doi = "10.1016/j.cell.2021.02.053",
language = "English",
volume = "184",
pages = "2212--2228",
journal = "Cell",
issn = "0092-8674",
publisher = "Elsevier B.V.",
number = "8",
}
SDG 3 Good Health and Well-being